Tumor Microenvironment-Responsive Nanocarrier Based on VO_x Nanozyme Amplify Oxidative Stress for Tumor Therapy

The construction of a novel nanocarrier that can break the redox balance in tumor cell is a promising anti-tumor strategy. Herein, a tumor microenvironment (TME)-responsive nanocarrier VC@Lipo is rationally designed by embedding ultrasmall VOx nanozyme and photosensitizer chlorin e6 (Ce6) into liposomes. The size of VC@Lipo nanocarrier is approximate to 35 nm and can be degraded in the weakly acidic environment of TME. The VOx nanozyme exhibits peroxidase-like activity and generates highly toxic hydroxyl radical center dot OH through Fenton-like reaction and O-1(2) in the presence of H2O2 independent of light, and more O-1(2) can be generated by the photodynamic effect of Ce6. In addition, the VOx nanozyme can effectively deplete intracellular overexpressed glutathione (GSH) through redox reactions. In vivo experiments demonstrate that the nanocarrier shows excellent biocompatibility, presents the largest enrichment at the tumor site after 6 h of intravenous injection into mice with the highest tumor inhibition rate of 54.18% after laser irradiation. Compared with the single treatment mode, VC@Lipo shows the best synergistic effect of chemodynamic-photodynamic therapy. This work provides a new paradigm for nanocatalytic therapy of cancer and is expected to provide new ideas for precision medicine in cancer.